The current state of transplantation is limited by two essential problems. The first problem relates to the process of rejection which occurs to some extent in most transplants. The second problem involves the preservation of tissue both donor's and recipient's.
The process of rejection is related to the immunological properties of the recipient's and donor's tissue. These immunological properties can be divided into two areas; antibody-mediated humoral group and the cellular-mediated mechanisms. Humoral immunity involves antibody produced by B-lymphocytes. This antibody when combined with the antigen can lyse cells and tissues, produce inflammation, bind cytotoxic lymphocytes or alter the function of the tissue. The antibody can bind antigen and activate the complement system which produces and releases substances which attract inflammatory cells and increase vascular permeability. Phagocytic cells can bind to these substances and are activated to cause tissue destruction. In addition, the antibodies may bind to the tissue involved and inhibit function of that tissue. Some antibodies bind to an antigen or cell and attract a K-lymphocyte which destroys the antibody bound cell. This process is known as antibody-dependent cellular cytotoxicity.
Cellular immunity involves T-lymphocytes which when activated can destroy tissue. There are both helper and suppressor lymphocytes. The helper lymphocytes promote immunologic reactions while the suppressor lymphocytes impede these reactions. There also exist natural killer lymphocytes which also play a role in the rejection process.
In addition, in both the host and the recipient, the macrophages and other phagocytic cells aid the rejection process by assisting the antibody mediated and cellular mediated mechanisms.
There exist a number of methods to monitor the rejection process. The serum of the recipient is mixed with lymphocytes from the donor in the presence of complement to detect the presence of antibodies. Trypan blue and ethidium bromide tests have been used to detect cytotoxic antibodies. Other tests have been used to evaluate the lymphocyte populations in tissues. Immunologic studies include: lymphocyte mediated cyctotoxicity, complement dependent cytotoxicity, spontaneous blastogenesis, as well as myocardial biopsy. A number of other studies are currently used to try to monitor the rejection process. However, attempts to monitor and prevent or treat the rejection process have met with great difficulty. Consequently, it is the purpose of this instant invention to improve the process of transplantation.
In addition, attempts at preservation of the donor and recipient have gone through many stages. Initially perfusion of blood or immersion in ice was used for the tissue. Currently methods utilize cooling with agents to decrease the metabolism of the cells, i.e. cardiplegic solutions in cardiac allografts. However, preservation is limited at this time to 4-24 hours. The purpose of this instant invention is also to prolong the time and to increase the quality of tissue preservation.